A-MSC Therapy for Kidney Transplant Rejection

Overseen by Timucin Taner, MD, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Mayo Clinic

Disqualifiers: Nephrotic proteinuria, Uncontrolled arrhythmia, Malignancy, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing if injecting special cells from donated fat tissue into the kidney's main blood vessel can safely reduce inflammation and prevent rejection in patients with transplanted kidneys.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that anticoagulation (blood-thinning) medications can be safely interrupted for 3 days before the infusion and resumed a day after. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment Adipose-derived MSC for kidney transplant rejection?

Research shows that adipose-derived stem cells (ADSCs) have strong anti-inflammatory and immune-modulating effects, which can help reduce rejection in kidney transplants. Studies in rats and other models have demonstrated that these cells can improve transplant outcomes by interacting with the immune system to prevent rejection. ^{1 2 3 4 5}

Is A-MSC therapy safe for humans?

Research shows that adipose-derived mesenchymal stem cell (MSC) therapy is generally safe in humans, with no significant cellular toxicity or serious adverse events reported in studies. It has been used safely in various conditions, including kidney-related issues, without significant side effects. ^{1 6 7 8 9}

How is A-MSC therapy different from other treatments for kidney transplant rejection?

A-MSC therapy uses adipose-derived mesenchymal stromal cells, which are known for their strong anti-inflammatory and immune-modulating properties, making them potentially more effective in reducing immune response compared to traditional treatments. This therapy is unique because it involves using cells from fat tissue, which are more potent and easily accessible than those from bone marrow, and it aims to minimize the need for other immunosuppressive drugs. ^{1 2 4 10 11}

Research Team

Timucin Taner, MD, PhD

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for kidney transplant recipients who can consent, have had a recent biopsy showing rejection, stable renal function with eGFR > 30 ml/min, and specific inflammation or rejection signs in the biopsy. Excluded are those with severe heart conditions, vascular diseases, acute illnesses within 30 days, allergies to contrast agents, unwilling to use contraception for 12 months post-treatment, substance abuse issues, active COVID-19 or other infections like CMV or BK virus.

Inclusion Criteria

I understand the study and agree to participate.

Histologic Criteria for Eligibility: ABMR: microvascular inflammation scores for glomerulitis (g) and peritubular capillaritis (ptc) (g:1 or 2; ptc:1 or 2). Cellular rejection: tubulitis (t) (t:1or 2); interstitial inflammation (i) (i:1 or 2); intimal arteritis (v) (v: 1 or 2). Mixed ABMR and cellular rejection

My kidney function is stable, with creatinine levels not much higher than before my biopsy.

Exclusion Criteria

I have had high levels of protein in my urine multiple times in the last year.

Hemoglobin (Hb} ≤ 8 g/dL, Potassium (K) ≥ 5.5 mEq/dL, Alanine aminotransferase (ALT) ≥ 60 U/L, Hemoglobin A1C (HbA1c) ≥ 7%, International Normalized Ratio (INR) ≥ 2.0, Platelet count < 50 x 109/L (patients who receive a platelet transfusion to increase their platelet count will not be excluded)

NYHA Class 3-4 CHF, Uncontrolled arrhythmia, Cerebrovascular accident (CVA) within 90 days of screening, Peripheral Arterial Disease (PAD), Acute illness within 30 days of screening, History of allergy or intolerance to iodinated contrast agents, Women of childbearing potential or male subjects with female partners of childbearing potential unwilling to use an effective method of contraception during and for 12 months post-treatment, History of or current evidence of alcohol abuse, illicit drug use or dependence, Active COVID 19 or positive test for the SARS-CoV-2 virus, History of malignancy within 5 years of enrollment, Serologic evidence of human immunodeficiency virus 1 or 2 infection, Epstein Barr Virus (EBV) sero-negativity (EBV naïve), Cytomegalovirus (CMV) sero-negativity, Active post-transplant opportunistic infections at the time of screening (CMV, BK virus, polyoma virus, EBV), Active Hepatitis B or Hepatitis C infection (e.g. NAT positive), and/or HBV core antibody positivity, Have received a kidney transplant from a Hepatitis C positive donor and plan to receive anti-viral treatment after transplant, Any chronic condition for which anti-coagulation cannot be safely interrupted for kidney biopsy based on the CHA2DS2-VASc score of ≥ 6 risk stratum, Positive pregnancy test, Participation in any other studies that involved investigational drugs or regimens in the preceding year, Any other condition, in the investigator's judgment, that increases the risk of A-MSC infusion or prevents safe trial participation, Unwilling or unable to adhere to study requirements and procedures, Per Banff criteria category 6: the presence of other changes not considered to be caused by acute or chronic rejection, BK-Virus Nephropathy, Posttransplant Lymphoproliferative Disorder, Calcineurin Inhibitor Toxicity, Acute Tubular Injury, Recurrent Disease, De Novo Glomerulopathy (Other Than TG), Pyelonephritis or Drug-Induced Interstitial Nephritis

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an infusion of allogeneic adipose-derived mesenchymal stromal cells (allo-A-MSC) directly into the renal artery

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including monitoring for adverse events and kidney allograft rejection

1 year

Treatment Details

Interventions

• Adipose-derived MSC (Mesenchymal Stromal Cells)

Trial Overview The study tests if infusing different doses of adipose-derived mesenchymal stromal cells (A-MSC) into the renal artery can safely reduce inflammation and treat kidney transplant rejection. Participants will receive either a low dose or high dose of A-MSC directly into their transplanted kidney's blood supply.

Participant Groups

Group I: Low Dose Group Experimental Treatment 1 Intervention

Adult kidney transplant recipients with subclinical rejection (biopsy-proven antibody-mediated and/or cellular rejection, including borderline rejection) will be administered one low dose of allogeneic A-MSC.

Group II: High Dose Group Experimental Treatment 1 Intervention

Adult kidney transplant recipients with subclinical rejection (biopsy-proven antibody-mediated and/or cellular rejection, including borderline rejection) will be administered one high dose of allogeneic A-MSC.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Dr. Gianrico Farrugia

Mayo Clinic

Chief Executive Officer since 2019

MD from University of Malta Medical School

Dr. Richard Afable

Mayo Clinic

Chief Medical Officer

MD from Loyola Stritch School of Medicine

Findings from Research

Adipose tissue-derived mesenchymal stem cells (MSCs) maintain their anti-inflammatory and immune-modulating properties even in the presence of human kidney disease or uremic serum, suggesting they could be effective in treating kidney conditions.

The potential for using autologous (patient-derived) adipose tissue-derived MSCs in clinical settings highlights the need for further research to establish their long-term safety and efficacy in kidney disease treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adipose tissue-derived mesenchymal stem cells: a fat chance of curing kidney disease? Lin, F.[2023]

Adipose tissue-derived stem cells (ADSCs) significantly reduced kidney transplant rejection in rats, leading to prolonged graft survival and decreased infiltration of T cells, indicating their potential as an effective immunomodulatory treatment in organ transplantation.

The mechanism of action involves ADSCs increasing the production of TSG-6, a protein that suppresses T cell activation and infiltration, thereby enhancing the anti-inflammatory response during kidney transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adipose tissue-derived stem cells suppress acute cellular rejection by TSG-6 and CD44 interaction in rat kidney transplantation. Kato, T., Okumi, M., Tanemura, M., et al.[2022]

Adipose-derived stem cells (ADSCs) isolated from renal adipose capsules proliferate faster and in greater numbers compared to those from groin adipose tissues, suggesting they are a more effective source for potential kidney disease treatments.

The study found that renal ADSCs have a lower expression of CD44 compared to groin ADSCs, indicating distinct biological characteristics that may influence their therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Study on the biological characteristics of adipose stem cells derived from renal adipose capsule cultured in vitro]. Wu, W., Zheng, HG., Zhang, DW., et al.[2010]

In a study involving 285 patients, co-infusion of donor adipose-derived mesenchymal stem cells (AD-MSC) and hematopoietic stem cells (HSC) during kidney transplantation was found to be safe and effective in minimizing immunosuppression, with the best outcomes observed in the group receiving both cell types.

At 1 and 5 years post-transplant, the group receiving AD-MSC + HSC showed the highest patient and graft survival rates, along with fewer rejection episodes and lower immunosuppression requirements compared to the control group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Co-infusion of donor adipose tissue-derived mesenchymal and hematopoietic stem cells helps safe minimization of immunosuppression in renal transplantation - single center experience. Vanikar, AV., Trivedi, HL., Kumar, A., et al.[2022]

In a dose escalation study involving 21 subjects, adipose-derived human mesenchymal stem cell (MSC) therapy showed no significant cellular or renal toxicity, indicating a favorable safety profile.

The therapy led to improvements in renal oxygenation and glomerular filtration rate, along with a reduction in inflammatory markers, suggesting potential efficacy in treating renovascular disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving human kidney function in renovascular disease with mesenchymal stem cell therapy. Sivanathan, KN., Coates, PT.[2020]

Adipose-derived mesenchymal stem cells (AD-MSC) significantly protect against kidney injury caused by 45 minutes of renal ischemia followed by 48 hours of reperfusion in rats, as evidenced by improved serum creatinine and blood urea nitrogen levels.

Histological analysis revealed that AD-MSC treatment reduced tubular necrosis and other signs of kidney damage, indicating their potential as a therapeutic intervention for acute kidney injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of adipose-derived mesenchymal stem cells on renal function and histopathology in a rat model of ischemia-reperfusion induced acute kidney injury. Changizi-Ashtiyani, S., Hafazeh, L., Ghasemi, F., et al.[2022]

The study evaluated the safety and efficacy of autologous adipose-derived stem cell (ASC) therapies in 17 patients with severe conditions, finding no serious adverse events over a follow-up period of up to 54 months.

Both ASC-derived products—a scaffold-free osteogenic graft for bone non-union and a biological dressing for chronic wounds—were successfully manufactured and implanted without contamination or genomic issues, demonstrating their feasibility for clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human Adipose-Derived Mesenchymal Stem Cells in Cell Therapy: Safety and Feasibility in Different "Hospital Exemption" Clinical Applications. Vériter, S., André, W., Aouassar, N., et al.[2022]

Mesenchymal stromal cells (MSC) have shown promise in kidney transplantation, demonstrating safety and feasibility in initial clinical studies, with potential to reduce the need for immunosuppressive drugs.

Some patients treated with MSC therapy exhibited biomarkers indicating immunomodulation, leading to successful and safe complete discontinuation of immunosuppression in one case, highlighting the potential for personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mesenchymal stromal cells in kidney transplantation. Casiraghi, F., Remuzzi, G.[2021]

A 29-year-old male with end-stage renal disease successfully received a kidney transplant with the co-infusion of donor-derived mesenchymal stem cells and hematopoietic stem cells, leading to stable kidney function for over 3 years.

Remarkably, the patient has maintained normal kidney function without any immunosuppression for 2.5 years, showing no signs of rejection or donor-specific antibodies, suggesting that the stem cell therapy may have contributed to achieving transplantation tolerance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-transplant co-infusion of donor-adipose tissue derived mesenchymal stem cells and hematopoietic stem cells may help in achieving tolerance in living donor renal transplantation. Vanikar, AV., Trivedi, HL., Gopal, SC., et al.[2014]

References

1. United States pubmed.ncbi.nlm.nih.gov

Adipose tissue-derived mesenchymal stem cells: a fat chance of curing kidney disease? [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Adipose tissue-derived stem cells suppress acute cellular rejection by TSG-6 and CD44 interaction in rat kidney transplantation. [2022]

3. China pubmed.ncbi.nlm.nih.gov

[Study on the biological characteristics of adipose stem cells derived from renal adipose capsule cultured in vitro]. [2010]

4. England pubmed.ncbi.nlm.nih.gov

Co-infusion of donor adipose tissue-derived mesenchymal and hematopoietic stem cells helps safe minimization of immunosuppression in renal transplantation - single center experience. [2022]

5. Korea (South) pubmed.ncbi.nlm.nih.gov

Multiple Injections of Adipose-Derived Stem Cells Improve Graft Survival in Human-to-Rat Skin Xenotransplantation through Immune Modulation. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Improving human kidney function in renovascular disease with mesenchymal stem cell therapy. [2020]

7. Iran pubmed.ncbi.nlm.nih.gov

The effect of adipose-derived mesenchymal stem cells on renal function and histopathology in a rat model of ischemia-reperfusion induced acute kidney injury. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Effect of co-transplantation of mesenchymal stem cells and hematopoietic stem cells as compared to hematopoietic stem cell transplantation alone in renal transplantation to achieve donor hypo-responsiveness. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Human Adipose-Derived Mesenchymal Stem Cells in Cell Therapy: Safety and Feasibility in Different "Hospital Exemption" Clinical Applications. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Mesenchymal stromal cells in kidney transplantation. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Pre-transplant co-infusion of donor-adipose tissue derived mesenchymal stem cells and hematopoietic stem cells may help in achieving tolerance in living donor renal transplantation. [2014]